Limited knowledge is available regarding the neurocognitive mechanism of decision-making and impulse control as a function of addiction and recovery. Yet the time course of brain changes and cognitive function during addiction and recovery may be critical to our ability to rationally target new treatments. Built upon a long-term cohort of cocaine-dependent users that have been prospectively followed by the applicants for more than 12 years, this pilot study will explore neurocognitive mechanisms associated with stages of addiction and recovery. The project will use Magnetic Resonance Imaging (MRI) techniques to investigate structural areas of the brain known to play a key role in decision-making, impulse control, and reward processing, structural and functional connectivity of these regions, as well as the responses of these same key regions to decisions made by subjects under conditions of uncertainty. The volume and gray/white matter density of brain areas that are important for processing reward and emotional information, including the nucleus accumbens, amygdala, insular and somatosensory cortex, ventromedial prefrontal cortex, and anterior cingulate, will be quantified for each subject from high resolution MRI scans. In addition the fMRI BOLD responses of these regions will be measured when subjects perform decision-making tasks. DTI and resting state fMRI will allow us to assess structural and functional connectivity of the relevant brain regions. These measures will be compared across subjects at different stages of addiction and recovery to explore research questions regarding the length of abstinence from cocaine required for brain functioning to recover or approach normal. Specifically, we will compare (1) cocaine addicts versus non-cocaine-using or normal controls, and (2) those recovered at various stages versus those not recovered in terms of (a) brain volume and gray matter density in brain regions known to play a key role in processing emotional information and decision-making; (b) activity in neural systems belonging to the reflective system (e.g., the VMPFC, anterior cingulate); (c) activity in neural systems belonging to the impulsive system (e.g., amygdala, ventral striatum, insula) when these participants perform various decision-making tasks, (d) modulatory effects of insular activities, and (e) structural and functional connectivity of the relevant brain regions. The results of this project wll inform the development of a larger study to examine details on specific brain areas that are more directly affected by cocaine addiction and involved in the process of recovery, which will have implications for the development of cognitive training programs and medications that target the relevant brain structures. PUBLIC HEALTH RELEVANCE: Recovery from addiction is a slow process, and chronic relapse to drug abuse is a public health concern. The proposed study addresses this public health problem by improving our understanding of the time course of brain changes and cognitive function during addiction and recovery, which may suggest new treatments to promote early recovery or to speed up the recovery process.